Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disease and one of the leading causes of morbidity and mortality worldwide. It is characterized by persistent respiratory symptoms and airflow limitation due to abnormalities in the lower airway following consistent exposure to noxious particles or gases. Acute exacerbations of COPD (AECOPD) are characterized by increased cough, purulent sputum production, and dyspnea. The AECOPD is mostly associated with infection caused by common cold viruses or bacteria, or co-infections. Chronic and persistent infection by non-typeable Haemophilus influenzae (NTHi), a Gram-negative coccobacillus, contributes to almost half of the infective exacerbations caused by bacteria. This is supported by reports that NTHi is commonly isolated in the sputum from COPD patients during exacerbations. Persistent colonization of NTHi in the lower airway requires a plethora of phenotypic adaptation and virulent mechanisms that are developed over time to cope with changing environmental pressures in the airway such as host immuno-inflammatory response. Chronic inhalation of noxious irritants in COPD causes a changed balance in the lung microbiome, abnormal inflammatory response, and an impaired airway immune system. These conditions significantly provide an opportunistic platform for NTHi colonization and infection resulting in a “vicious circle.” Episodes of large inflammation as the consequences of multiple interactions between airway immune cells and NTHi, accumulatively contribute to COPD exacerbations and may result in worsening of the clinical status. In this review, we discuss in detail the interplay and crosstalk between airway immune residents and NTHi, and their effect in AECOPD for better understanding of NTHi pathogenesis in COPD patients.

BackgroundChronic suppurative otitis media (CSOM) is an important cause of hearing loss in children and constitutes a serious health problem globally with a strong association to resource-limited living conditions. Topical antibiotics combined with aural toilet is the first-hand treatment for CSOM but antimicrobial resistance and limited availability to antibiotics are obstacles in some areas. The goal of this study was to define aerobic pathogens associated with CSOM in Angola with the overall aim to provide a background for local treatment recommendations.MethodsSamples from ear discharge and the nasopharynx were collected and cultured from 152 patients with ear discharge and perforation of the tympanic membrane. Identification of bacterial species was performed with matrix-assisted laser desorption/ionization-time of flight mass spectrometry and pneumococci were serotyped using multiplex polymerase chain reactions. Antimicrobial susceptibility testing was done according to EUCAST.ResultsOne hundred eighty-four samples from ear discharge and 151 nasopharyngeal swabs were collected and yielded 534 and 289 individual isolates, respectively. In all patients, correspondence rate of isolates from 2 ears in patients with bilateral disease was 27.3% and 9.3% comparing isolates from the nasopharynx and ear discharge, respectively. Proteus spp. (14.7%), Pseudomonas aeruginosa (13.2%) and Enterococcus spp. (8.8%) were dominating pathogens isolated from ear discharge. A large part of the remaining species belonged to Enterobacteriaceae (23.5%). Pneumococci and Staphylococcus aureus were detected in approximately 10% of nasopharyngeal samples. Resistance rates to quinolones exceeded 10% among Enterobacteriaceae and was 30.8% in S. aureus, whereas 6.3% of P. aeruginosa were resistant.ConclusionsThe infection of the middle ear in CSOM is highly polymicrobial, and isolates found in nasopharynx do not correspond well with those found in ear discharge. Pathogens associated with CSOM in Angola are dominated by gram-negatives including Enterobacteriaceae and P. aeruginosa, while gram-positive enterococci also are common. Based on the results of antimicrobial susceptibility testing topical quinolones would be the preferred antibiotic therapy of CSOM in Angola. Topical antiseptics such as aluminium acetate, acetic acid or boric acid, however, may be more feasible options due to a possibly emerging antimicrobial resistance.Electronic supplementary materialThe online version of this article (10.1186/s40249-018-0422-7) contains supplementary material, which is available to authorized users.

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BackgroundIdentification and characterization of non-typeable Haemophilus influenzae (NTHi) with reduced susceptibility to β-lactam antibiotics due to mutations in penicillin binding protein 3 (PBP3) is a clinical challenge. We analyzed a blood isolate, NTHi93–57485, that was categorized as aminopenicillin resistant but lacked key amino acid substitutions in PBP3 that have previously been associated with reduced aminopenicillin susceptibility. The significance of an alternative amino acid substitution (Y528H) in this isolate was examined.ResultsSite-directed mutagenesis of a β-lactam susceptible H. influenzae (NTHi3655) was performed to introduce the Y528H substitution into wild-type ftsI (encoding for PBP3). Disc diffusion screening and broth microdilution determination of MICs for β-lactam agents were done with the NTHi3655-PBP3Y528H mutant and were compared with the NTHi3655 wild-type as well as the original clinical isolate NTHi93–57485. Introduction of the Y528H substitution in NTHi3655 resulted in positive screening for β-lactam resistance. MICs for aminopenicillins were increased in the mutant compared to the wild-type. However, the mutant remained susceptible to aminopenicillins according to EUCAST clinical breakpoints (assuming intravenous treatment) and the introduction of Y528H alone did not increase the resistance to the same level as NTHi93–57485. None of the isolates had frame shift insertions in the acrR gene regulating the AcrAB efflux pump.ConclusionsIn parallel to the previously well-described PBP3-substitutions R517H and N526K, we demonstrate that Y528H confers reduced aminopenicillin susceptibility.Electronic supplementary materialThe online version of this article (10.1186/s12866-018-1196-6) contains supplementary material, which is available to authorized users.

Key Points Exposure of P5 at the surface of NTHi positively correlates with C4BP binding. C4BP bound to the bacterial surface retains its complement inhibitory capacity. C4BP binding to P5 is important for NTHi serum resistance.